title: Influence of CCR5 and CCR2 genetic variants in the resistance/susceptibility to HIV in serodiscordant couples from Colombia.
abstract: The main genetic factor related to HIV-1 resistance is the CCR5-Δ32 mutation; however, the homozygous genotype is uncommon. The CCR5-Δ32 mutation along with single nucleotide polymorphisms (SNPs) in the CCR5 promoter and the CCR2-V64I mutation have been included in seven human haplogroups (HH) previously associated with resistance/susceptibility to HIV-1 infection and different rates of AIDS progression. Here, we determined the association of the CCR5 promoter SNPs, the CCR5-Δ32 mutation, CCR2-V64I SNP, and HH frequencies with resistance/susceptibility to HIV-1 infection in a cohort of HIV-1-serodiscordant couples from Colombia. Seventy HIV-1-exposed, but seronegative (HESN) individuals, 57 seropositives (SP), and 112 healthy controls (HC) were included. The CCR5-Δ32 mutation and CCR2-V64I SNP were identified by PCR, and the CCR5 promoter SNPs were evaluated by sequencing. None of the individuals exhibited a homozygous Δ32 genotype; the CCR2-I allele was more frequent in HESN (34%) than HC (23%) (p=0.039, OR=1.672). The frequency of the 29G allele was higher in SP than HC (p=0.003, OR=3). HHF2 showed a higher frequency in HC (19%) than SP (9%) (p=0.027), while HHG1 was more frequent in SP (11.1%) than in HC (4.2%) (p=0.019). The AGACCAC-CCR2-I-CCR5 wild-type haplotype showed a higher frequency in SP (14.2%) than in HC (3.7%) (p=0.001). In conclusion, the CCR5-Δ32 allele is not responsible for HIV-1 resistance in this HESN group; however, the CCR2-I allele could be protective, while the 29G allele might increase the likelihood of acquiring HIV-1 infection. HHG1 and the AGACCAC-CCR2-I-CCR5 wild-type haplotype might promote HIV-1 infection while HHF2 might be related to resistance. However, additional studies are required to evaluate the implications of these findings.
authors.affiliation: 1 Grupo Inmunovirología, Universidad de Antioquia , Medellín, Colombia .
authors.forename: Wildeman
authors.initials: W
authors.lastname: Zapata
authors.forename: Wbeimar
authors.initials: W
authors.lastname: Aguilar-Jiménez
authors.forename: Nicolás
authors.initials: N
authors.lastname: Pineda-Trujillo
authors.forename: Winston
authors.initials: W
authors.lastname: Rojas
authors.forename: Hernando
authors.initials: H
authors.lastname: Estrada
authors.forename: María T
authors.initials: MT
authors.lastname: Rugeles
mesh_terms: D001483:Base Sequence; D003105:Colombia; D017931:DNA Primers; D024882:Drug Resistance, Viral; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D054390:Receptors, CCR2 / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*; D012747:Sexual Partners
chemical_list: C515334:CCR2 protein, human; C584933:CCR5 protein, human; D017931:DNA Primers; D054390:Receptors, CCR2; D019713:Receptors, CCR5